Reframing Formalin: A Molecular Opportunity Enabling Historical Epigenomics and Retrospective Gene Expression Studies.

Formalin preservation of museum specimens has long been considered a barrier to molecular research due to extensive crosslinking and chemical modification. However, recent optimisation of hot alkaline lysis and proteinase K digestion DNA extraction methods have enabled a growing number of studies to overcome these challenges and conduct genome-wide re-sequencing and targeted locus-specific sequencing. The newest, and perhaps most unexpected utility of formalin preservation in archival samples is its ability to preserve in situ DNA-protein interactions at a molecular level.

Colorectal Cancer Screening and Social Needs.

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. While patient-reported barriers have been previously described, few studies have analyzed how patients' social needs affect screening rates.

Methods: This cross-sectional study includes 3,443 Kaiser Permanente (KP) patients ages 50 to 75 years who completed the 2020 KP National Social Needs Survey.

Cervical Cancer Screening: Patient Perspectives on Transitioning to Primary High-Risk Human Papillomavirus Testing Alone.

Introduction: In 2018, the US Preventive Services Task Force updated cervical cancer screening recommendations to allow for screening every 5 years with primary human papillomavirus (HPV) testing in combination with cytology (cotesting) or every 5 years with primary HPV screening alone. Despite these changes, the uptake of primary HPV screening has been lower than expected. The purpose of this study was to evaluate the patient perspective of an integrated health system transition from cotesting to primary HPV testing among a 30- to 65-year-old cohort.

What value do teaching hospitals provide commercial beneficiaries when in an ACO?

Objectives: The number of commercial beneficiaries cared for by accountable care organizations (ACOs) is growing, but the literature examining their trends is nascent.

Study Design: We examined commercial claims data from 2019 to 2021 to compare beneficiaries attributed to participants in Medicare Shared Savings Program ACOs with and without a major teaching hospital.

Methods: We calculated mortality and spending by setting for each ACO type by year.

A Patient-Centered Conceptual Model of AYA Cancer Survivorship Care Informed by a Qualitative Interview Study.

: Conceptual models provide frameworks to illustrate relationships among patient-, provider-, system-, and community-level factors that inform care delivery and research. Existing models of cancer survivorship care focus largely on pediatric or adult populations whose needs differ from adolescents and young adults (AYAs). We developed a patient-centered conceptual model of AYA survivorship care.

Primary Human Papillomavirus Screening: Women's Perceptions of New Cervical Cancer Screening Recommendations.

Current clinical guidelines recommended primary human papillomavirus (HPV) screening for cervical cancer testing. Previous studies reported patient-level barriers (e.g.

Century-old chromatin architecture revealed in formalin-fixed vertebrates.

Gene expression is regulated by changes in chromatin architecture intrinsic to cellular differentiation and as an active response to environmental stimuli. Chromatin dynamics are a major driver of phenotypic diversity, regulation of development, and manifestation of disease. Remarkably, we know little about the evolutionary dynamics of chromatin reorganisation through time, data essential to characterise the impact of environmental stress during the ongoing biodiversity extinction crisis (20-21 century).

Patterns of Care Following a Positive Fecal Blood Test for Colorectal Cancer: A Mixed Methods Study.

Background/objective: Multilevel barriers to colonoscopy after a positive fecal blood test for colorectal cancer (CRC) are well-documented. A less-explored barrier to appropriate follow-up is repeat fecal testing after a positive test. We investigated this phenomenon using mixed methods.

Late endocrine diseases in survivors of adolescent and young adult cancer in California: a population-based study.

Background: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level.

Methods: We used data from the California Cancer Registry (2006-2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15-39 years) who survived ≥2 years after diagnosis.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

Introduction: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors.

Methods: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years.

Hot alkaline lysis gDNA extraction from formalin-fixed archival tissues.

Formalin fixation of natural history specimens and histopathological material has historically been viewed as an impediment to successful genomic analysis. However, the development of extraction methods specifically tailored to contend with heavily crosslinked archival tissues, re-contextualises millions of previously overlooked specimens as viable molecular assets. Here, we present an easy-to-follow protocol for screening archival wet specimens for molecular viability and subsequent genomic DNA extraction suitable for sequencing.

Unsatisfactory Fecal Immunochemical Tests for Colorectal Cancer Screening: Prevalence, Reasons, and Subsequent Testing.

Background: Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling.

Methods: Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019.

Using Machine Learning to Leverage Biomarker Change and Predict Colorectal Cancer Recurrence.

Purpose: The risk of colorectal cancer (CRC) recurrence after primary treatment varies across individuals and over time. Using patients' most up-to-date information, including carcinoembryonic antigen (CEA) biomarker profiles, to predict risk could improve personalized decision making.

Methods: We used electronic health record data from an integrated health system on a cohort of patients diagnosed with American Joint Committee on Cancer stage I-III CRC between 2008 and 2013 (N = 3,970) and monitored until recurrence or end of follow-up.

Incidence and Survival for Patients Diagnosed With Breast, Colorectal, and Lung Cancer in an Integrated System.

Introduction: Documenting trends in cancer incidence and survival is a national priority. This study estimated age- and sex-adjusted incidence and 5-year relative survival among patients with cancer diagnosed within Kaiser Permanente compared to Surveillance, Epidemiology, and End Results (SEER) estimates.

Methods: The cohort included Kaiser Permanente health plan members diagnosed with breast (BC), colorectal (CRC), or lung cancer (LC) between January 1, 1999 and December 31, 2018.

Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S.

Barriers and facilitators to implementation and sustainment of guideline-recommended depression screening for patients with breast cancer in medical oncology: a qualitative study.

Objectives: Implementation of guideline-recommended depression screening in oncology presents numerous challenges. Implementation strategies that are responsive to local context may be critical elements of adoption and sustainment. We evaluated barriers and facilitators to implementation of a depression screening program for breast cancer patients in a community medical oncology setting as part of a cluster randomized controlled trial.

Racial and Ethnic Bias in Risk Prediction Models for Colorectal Cancer Recurrence When Race and Ethnicity Are Omitted as Predictors.

Importance: Including race and ethnicity as a predictor in clinical risk prediction algorithms has received increased scrutiny, but there continues to be a lack of empirical studies addressing whether simply omitting race and ethnicity from the algorithms will ultimately affect decision-making for patients of minoritized racial and ethnic groups.

Objective: To examine whether including race and ethnicity as a predictor in a colorectal cancer recurrence risk algorithm is associated with racial bias, defined as racial and ethnic differences in model accuracy that could potentially lead to unequal treatment.

Design, Setting, And Participants: This retrospective prognostic study was conducted using data from a large integrated health care system in Southern California for patients with colorectal cancer who received primary treatment between 2008 and 2013 and follow-up until December 31, 2018.

Underutilization or appropriate care? Assessing adjuvant chemotherapy use and survival in 3 heterogenous subpopulations with stage II/III colorectal cancer within a large integrated health system.

Clinical guidelines have recommended adjuvant chemotherapy (ACT) for patients with high-risk stage II colon cancer, although the survival benefit is unclear. ACT is also recommended for patients with stage III colon cancer to reduce the risk of recurrence and mortality. For stage II/III rectal cancer, however, the role of perioperative chemotherapy (PCT, adjuvant or neoadjuvant) remains controversial, resulting in substantial variation in its use in clinical practice.

Racial Disparities in the Ascertainment of Cancer Recurrence in Electronic Health Records.

Purpose: There is growing interest in using computable phenotypes or proxies to identify important clinical outcomes, such as cancer recurrence, in rich electronic health records data. However, the race/ethnicity-specific accuracies of these proxies remain unclear. We examined whether the accuracy of a proxy for colorectal cancer (CRC) recurrence differed by race/ethnicity and the possible mechanisms that drove the differences.

Trends in sepsis and pneumonia during COVID-19: lessons from BPCIA.

Objectives: The COVID-19 pandemic affected care delivery nationwide for all patients, influencing cost and utilization for patients both with and without COVID-19. Our first analysis assessed changes in utilization for patients with sepsis without COVID-19 prior to vs during the pandemic. Our second analysis assessed cost and utilization changes during the pandemic for patients with sepsis or pneumonia both with and without COVID-19.

Succeeding in Medicare's newest bundled payment program: Results from teaching hospitals.

Background: In 2018, Medicare implemented a successor to its Bundled Payments for Care Improvement (BPCI) program, BPCI Advanced, with stricter participation rules and new financial incentives to reduce spending.

Methods: Using claims-based episode data from thirteen participants, we compared spending and utilization in the first fifteen months of the new program (October 2018 to December 2019) to hospital- and episode-specific target prices, with a deep dive into clinical correlates for the most commonly-selected clinical episodes, sepsis and congestive heart failure.

Results: Twelve out of thirteen participants in a collaborative of teaching hospitals achieved shared savings for both Medicare and their own institution.

A study protocol for a cluster randomized pragmatic trial for comparing strategies for implementing primary HPV testing for routine cervical cancer screening in a large health care system.

Background: Limited guidance exists regarding implementation strategies that best facilitate cancer screening practice substitution and achieve optimal stakeholder-centered outcomes. Here we describe the protocol for a randomized pragmatic trial comparing two implementation strategies to facilitate substitution of primary HPV screening for Pap and HPV co-testing to perform routine cervical cancer screening of women aged 30-65 years at Kaiser Permanente Southern California (KPSC).

Methods: Twelve service areas within KPSC will be randomized to a "centrally-administered system-wide implementation + local-tailored implementation" strategy or a "centrally-administered system-wide implementation only" strategy.

Trends in HPV vaccine administration and HPV vaccine coverage in children by race/ethnicity and socioeconomic status during the COVID-19 pandemic in an integrated health care system in California.

Background: We sought to evaluate the trends of HPV vaccination between 03/2019-09/2021 and whether the impact of the COVID pandemic on HPV vaccination varied by race/ethnicity and neighborhood deprivation index (NDI).

Methods: Electronic medical records at Kaiser Permanente Southern California were used to assess monthly volume of HPV vaccine doses administered among children aged 9-12.9yrs, and up-to-date coverage (% vaccinated) by age 13 between 03/2019-09/2021.